The increased awareness of the importance of normal growth, as well as an increased aesthetic interest, in infants and adolescents has led to an increased public interest in height growth. In the past, height growth was thought to depend on heredity. However, it is said that the proportion to which heredity is responsible for actual height growth is only 23%, and also, depending on the care during the period of growth, sufficient height growth can be achieved. Therefore, a great deal of money is being invested, estimated to be anywhere between 4-100 million dollars, to achieve height growth within the time period in which the growth plate is not closed. A public opinion survey shows that 33% of children in this growth period receive artificial care for height growth. Thus, there is also a growing number of therapeutic agents for growth, or hospitals that run growth clinics. However, most of the drugs that are currently in the market simply contain nutritional supplement components, and a question remains as to the proportion of therapeutic agents for growth that produce a real effect. Furthermore, virtually no drug has a target directly related to height growth. The Fair Trade Commission reports that even though the majority of therapeutic agents for growth that are distributed in the market are simply general food products or functional food products, they are labeled with terms such as “agent for height growth” or “(functional) food product for height growth.” Developing a novel therapeutic agent for growth is therefore critical at this point, where proper therapeutic agents for growth are still lacking, in spite of consumption trends.
Meanwhile, height growth necessitates an increase in bone length, and endochondral ossification is associated with such an increase. Ossification can be largely classified as intramembraneous ossification and endochondral ossification. Intramembraneous ossification is a formation of bones in which calcium and phosphorus secreted from the osteoblasts are lumped together and gradually increase in size. It occurs in the periosteum on the outer surface of the bone edge, and relates to the increase in bone thickness. On the other hand, endochondral ossification is a formation of bones in which a cartilage model is formed and then an ossification center emerges at its center. This occurs in the epiphyseal plate and relates to the increase in longitudinal bone length. That is, the increase in bone thickness and that in bone length are caused by different ossification processes. Endochondral ossification is largely induced by endocrine factors and paracrine factors. Growth hormone injection, which is a drug that can stimulate the endocrine factors, is available to date. However, growth hormone injection is not suitable for a child with normal hormone secretion, and instead produces side effects when used, such as hypothyroidism and hyperpituitarism. Moreover, it is not easily accessible because of its high cost. In addition, a recent issue concerns precocious puberty causing early closure of the growth plate, thus shortening the period of growth. Since paracrine factors are involved in the actual closure of the growth plate, it can be said that targeting them is important for enhancing the effect of related drugs. Hence, the present inventors have investigated the Wnt/β-catenin signaling pathway, which is activated by Wnt, one of the paracrine factors that are involved in the increase in bone length, and found that the increase in longitudinal bone length is induced by indirubin-3′-oxime, one of the substances that activate β-catenin, which is a core signal transducer in this signaling pathway. The present inventors also sought to utilize the substance to induce height growth. Indirubin-3′-oxime was synthesized as a derivative of indirubin, a component found in the roots or leaves of indigo plants, used for the Chinese medicine, Danggui Longhui Wan. It is also known to be free of toxicity. The present inventors have found that indirubin-3′-oxime, in particular, activates the growth plate by stimulating chondrocytes, which are involved in height growth, in the growth plate. Unlike conventional therapeutic agents for growth, indirubin-3′-oxime regulates the signaling pathway based on specific targets involved in height growth, and is therefore effective in inducing height growth specifically. Furthermore, because indirubin, which is the source substance for indirubin-3′-oxime, is a low molecular weight compound that has already reached the second stage of clinical trial as a therapeutic agent for leukemia, its safety is more or less guaranteed. Moreover, the development cost for indirubin-3′-oxime is relatively low. Thus, the expected effect is very large for utilizing indirubin-3′-oxime as a therapeutic agent for height growth.